Ask about this productRelated genes to: HDAC8 antibody
- Gene:
- HDAC8 NIH gene
- Name:
- histone deacetylase 8
- Previous symbol:
- HDACL1, WTS, MRXS6
- Synonyms:
- RPD3, KDAC8
- Chromosome:
- Xq13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-28
- Date modifiied:
- 2019-02-19
Related products to: HDAC8 antibody
Related articles to: HDAC8 antibody
- KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) is an aggressive AML subtype characterized by 11q23 chromosomal rearrangements involving KMT2A gene and clinically associated with poor prognosis. Herein, we show that HDAC8 is upregulated in KMT2A-r AML and high HDAC8 is associated with poor overall survival in KMT2A-r AML patients. Using a KMT2A::MLLT3 mouse model, we demonstrate that both genetic knockout and pharmacological inhibition of HDAC8 significantly delayed leukemia progression, prolonged survival and reduced disease recurrence. Mechanistically, HDAC8 inhibition downregulates STAT3-MYC axis independent of TP53 status across AML genetic subtypes. Biochemical assays revealed that HDAC8 binds directly to STAT3, promoting its deacetylation and stabilization, while HDAC8-selective inhibitor (HDAC8i) treatment results in increased STAT3 acetylation and subsequent STAT3 degradation which in turn downregulates MYC. Given that STAT3-MYC signaling promotes cell survival and Venetoclax resistance, we show that HDAC8i exhibits synergistic anti-leukemia activity with Venetoclax in primary AML cells regardless of TP53 status. Combination of HDAC8i and Venetoclax synergistically reduced leukemia burden and significantly prolonged survival in both KMT2A::MLLT3 AML and patient-derived xenograft models. This study highlights the regulatory function of HDAC8 on STAT3-MYC and provides the proof-of-principle for targeting HDAC8 in combination with Venetoclax for the treatment of KMT2A-r AML. - Source: PubMed
Publication date: 2026/04/21
Zhang LianjunGuo WanchengFu Yu-HsuanWu DijiongLi ManChen Ying-ChiehTseng Chi-YangHua Wei-KaiNguyen Le Xuan TruongHe XinDong HaojieZhang LeiZhang BinLi LingMarcucci GuidoKuo Ya-Huei - - Source: PubMed
Publication date: 2026/04/15
Mishra SujataA Sai Ananya PavaniVema AparnaKalle Arunasree M - In livestock, understanding the genetic basis of adaptation to the environment is essential for enhancing resilience to climate change and sustaining productivity in diverse environments. Indigenous Ethiopian cattle represent an ideal model for such studies, as they have evolved across a wide range of environments from the cool, oxygen-limited highlands to the hot, pathogen-rich lowlands. These environmental gradients imposed intense selective pressures, shaping their genomic landscape. In this study, we performed the first comprehensive analysis of X-linked adaptive signatures in Ethiopian indigenous cattle using whole-genome sequencing data. - Source: PubMed
Publication date: 2026/04/10
Ayalew WondossenTarekegn Getinet MXiaoyun WuChu MinNaboulsi RakanTessema Tesfaye SBongcam-Rudloff ErikNegussie EnyewPing YanZhang Zhe - The role of epigenetic regulation in HIV latency remains incompletely understood. We show that histone deacetylase 3 (HDAC3) inhibits trans-activator of transcription (Tat)-mediated HIV transcription through histone decrotonylation (HDCR), independent of deacetylase activity. Chemical biology approaches identified selective HDCR inhibitors (HDCRis) that reverse HIV latency with minimal impact on other histone acylations. Although HDAC2, HDAC3, and HDAC8 exhibit HDCR activity, genetic and chemical studies reveal that the HDCRi citarinostat is selective for HDAC3 and HDAC8. Molecular docking suggests that HDCRi binds outside the zinc-binding pocket, distinct from the classical HDAC inhibitor vorinostat (SAHA, suberoylanilide hydroxamic acid). Key residues (arginine-265, arginine-301, glutamine-113, and aspartic acid-57) are essential for HDCR selectivity, as their mutation abolishes HDCR activity and increases histone crotonylation without altering other acylation marks. Citarinostat increases histone crotonylation at the HIV long terminal repeat, robustly activating HIV transcription in cell lines, primary CD4 T cells, and brain microglia from simian immunodeficiency virus-infected nonhuman primates and participants enrolled in the Last Gift rapid research autopsy cohort, highlighting HDCR as a promising therapeutic target for HIV latency. - Source: PubMed
Publication date: 2026/04/10
Li XiaoyiLi DajiangTang YuyangNearing MarieVarco-Merth BenjaminChen HongjieSmith DaveyGianella SaraArchin Nancie MOkoye Afam ADandekar SatyaMargolis David MChirasani Venkat RGumpper Ryan HJiang Guochun - Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that affects almost any organ, including the central nervous system. It leads to a wide range of neurodevelopmental delays, and there are currently no available clinical treatments. CdLS is caused by pathogenic variants in one of the 7 genes coding for the cohesin complex, a multimeric structure responsible for sister chromatid cohesion, or for cohesin ring-interacting proteins. Additionally, altered regulation of molecular pathways during development, including the canonical WNT pathway, can cause CdLS malformations. In our study, we evaluated the positive effects of using lithium as an activator of the canonical WNT pathway to ameliorate neural CdLS phenotype. We have exploited accurate two-dimensional (2D) and three-dimensional (3D) human central nervous system in vitro models representing disease-related neurobiological phenotypes: induced pluripotent stem cells of human origin (hiPSCs) differentiated into neural precursors, neurons, and brain organoids (BOs). CdLS models demonstrate alterations in proliferation and differentiation capabilities when mimicking HDAC8 haploinsufficiency. Furthermore, RNA-seq analysis of BOs revealed that both neuronal differentiation and the WNT pathway are downregulated when treated with the HDAC8 inhibitor alone. Following lithium treatment, cells show an enhanced ability to differentiate into the neuronal lineage. Additionally, our working hypothesis is that a specific mechanism may exist that, by connecting lipid metabolism, canonical WNT pathway, and cell death, results in typical CdLS neurodevelopmental deficits. - Source: PubMed
Publication date: 2026/03/28
Parodi ChiaraLettieri AntonellaGrazioli PaoloDi Fede ElisabettaGrassi SaraTaci EsiToscani AndreaPrioni SimonaRebellato StefanoColombo Elisa AdeleRasetti SilviaCutarelli AlessandroMariani MilenaCorti StefaniaFinelli PalmaPrinetti AlessandroFazio GraziaSelicorni AngeloConti LucianoGervasini CristinaMassa Valentina